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- Title
- Cholera toxin activates the unfolded protein response through an adenylate cyclase-independent mechanism.
- Creator
-
Vanbennekom, Neyda, Teter, Kenneth, Tatulian, Suren, Jewett, Mollie, Zervos, Antonis, University of Central Florida
- Abstract / Description
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Cholera toxin (CT) is a bacterial protein toxin responsible for the gastrointestinal disease known as cholera. CT stimulates its own entry into intestinal cells after binding to cell surface receptors. Once internalized, CT is delivered via vesicle-mediated transport to the endoplasmic reticulum (ER), where the CTA1 subunit dissociates from the rest of the toxin and is exported (or translocated) into the cytosol. CTA1 translocates from the ER lumen into the host cytosol by exploiting a host...
Show moreCholera toxin (CT) is a bacterial protein toxin responsible for the gastrointestinal disease known as cholera. CT stimulates its own entry into intestinal cells after binding to cell surface receptors. Once internalized, CT is delivered via vesicle-mediated transport to the endoplasmic reticulum (ER), where the CTA1 subunit dissociates from the rest of the toxin and is exported (or translocated) into the cytosol. CTA1 translocates from the ER lumen into the host cytosol by exploiting a host quality control mechanism called ER-associated degradation (ERAD) that facilitates the translocation of misfolded proteins into the cytosol for degradation. Cytosolic CTA1, however, escapes this fate and is then free to activate its target, heterotrimeric G-protein subunit alpha (Gs?), leading to adenlyate cyclase (AC) hyperactivation and increased cAMP concentrations. This causes the secretion of chloride ions and water into the intestinal lumen. The result is severe diarrhea and dehydration which are the major symptoms of cholera. CTA1's ability to exploit vesicle-mediated transport and ERAD for cytosolic entry demonstrates a potential link between cholera intoxication and a separate quality control mechanism called the unfolded protein response (UPR), which up-regulates vesicle-mediated transport and ERAD during ER stress. Other toxins in the same family such as ricin and Shiga toxin were shown to regulate the UPR, resulting in enhanced intoxication.Here, we show UPR activation by CT, which coincides with a marked increase in cytosolic CTA1 after 4 hours of toxin exposure. Drug induced-UPR activation also increases CTA1 delivery to the cytosol and increases cAMP concentrations during intoxication. We investigated whether CT stimulated UPR activation through Gs? or AC. Chemical activation of Gs? induced the UPR and increased CTA1 delivery to the cytosol. However, AC activation did not increase cytosolic CTA1 nor did it activate the UPR. These data provide further insight into the molecular mechanisms that cause cholera intoxication and suggest a novel role for Gs? during intoxication, which is UPR activation via an AC-independent mechanism.
Show less - Date Issued
- 2013
- Identifier
- CFE0004951, ucf:49560
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0004951
- Title
- PUBS, PUNTERS, AND PINTS: ANTHROPOLOGICAL REFLECTIONS ON PUB LIFE IN IRELAND.
- Creator
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Cucchiara, Jason, Matejowsky, Ty, University of Central Florida
- Abstract / Description
-
Ireland is a country with a rich and unique cultural heritage. It is difficult to imagine that certain facets of Irish culture (e.g. Saint Patrick's Day, the Blarney Stone, or the Ring of Kerry) can ever be taken for granted since they are so widely recognized internationally. One common feature of Irish life that possibly warrants more scholarly attention is the public house or pub. Much has been written about pubs as quaint institutions in popular literature and fiction. Curiously, they...
Show moreIreland is a country with a rich and unique cultural heritage. It is difficult to imagine that certain facets of Irish culture (e.g. Saint Patrick's Day, the Blarney Stone, or the Ring of Kerry) can ever be taken for granted since they are so widely recognized internationally. One common feature of Irish life that possibly warrants more scholarly attention is the public house or pub. Much has been written about pubs as quaint institutions in popular literature and fiction. Curiously, they remain largely overlooked as vital aspects of Irish culture by anthropologists and others in the social sciences. In many ways, socio-cultural research on pub life in Ireland is woefully under examined. In an effort to better evaluate the significance of traditional pub life to Irish culture, my thesis seeks to integrate and critically assess the existing socio-cultural literature on Irish pub life. Such work will not only help highlight both the commonalities and discrepancies within this area of study, it will more significantly identify those areas of Irish pub life that can benefit from further academic investigation. Two recent trips to Ireland in September 2004 and May 2006, allowed me to observe important aspects of pub life first hand. It became apparent from these encounters that, like the history of Ireland itself, local pubs have a rich historical foundation. Many of the pubs that I visited have been in existence or operational since the Middle Ages. Based on this longevity, one can reasonably argue that pubs in Ireland function largely as locales of social significance and cultural reproduction, not just centers of recreational drinking. Using my travel experience as a starting point for the critical analysis phase of this thesis project, I have developed three general research questions that I will explore to varying degrees in the context of this work. These are: (1) what are the origins of pubs in Ireland?; (2) what explicit and implicit functions do pubs serve in Irish communities?; and (3) what possible developments are likely to affect Irish pubs in the near and distant future?
Show less - Date Issued
- 2009
- Identifier
- CFE0002578, ucf:48255
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0002578
